Background: Hepatocellular carcinoma (HCC) is a global health problem. HCC is the fourth common malignancy in Egypt. It is a crucial medical need to predict hepatocellular carcinoma development in cirrhotic liver patients. Objectives: this study aims to investigate the association between TLR4 gene polymorphism (rs2149356) and the probability of HCC development among chronic hepatitis C virus infected patients and clarify the role of serum IL-17 in patients with end stage liver disease and HCC in HCV infected patients. Methodology: the study included 25 patients with chronic hepatitis C infection, 25 patients with chronic hepatitis C infection and HCC, and 25 apparently healthy control subjects as controls. All participants undergone full clinical and laboratory assessment. TLR4 (rs2149356) G/T polymorphism genotyping by PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) and serum IL-17 detection by ELISA (enzyme-linked immunosorbent assay). Results: TLR4 (rs2149356) GG genotype was significantly associated with chronic HCV with HCC patients (72%) and chronic HCV patients (48%), while GT genotype was associated with healthy controls (48%) (P-value